VANCOUVER, B.C. — The latest Cochrane systematic review of digoxin for treatment of heart failure patients in sinus rhythm paints a picture of a more than 200-year-old drug that's still clinically useful, although it has no effect on mortality, William B. Hood Jr., M.D., said at a meeting sponsored by the International Academy of Cardiology.
“It's probably not first-line therapy. It's not very powerful. But it's available for patients who are not fully responsive to other agents that have become first-line treatments—the ACE inhibitors, β-blockers, spironolactone, and the angiotensin receptor blockers,” added Dr. Hood, lead author of the recent Cochrane review and a cardiologist at the University of Washington, Seattle.
The metaanalysis was restricted to randomized, double-blind, placebo-controlled trials involving adults followed for at least 7 weeks. Thirteen trials totaling nearly 7,900 patients qualified, including the largest of all digoxin studies: the 6,800-patient, 3-year Digitalis Investigation Group (DIG) trial (N. Engl. J. Med. 1997;336:525–33).
Why even bother doing a metaanalysis when one trial is so dominant? Dr. Hood explained that the smaller trials are helpful in that each consistently reached the same conclusion as DIG regarding the effect of digoxin on mortality—namely, there is none. The drug didn't lessen mortality, nor did it significantly worsen it.
In the DIG trial, however, there was a nonsignificant trend for fewer deaths from heart failure in digoxin-treated patients and a hint that the inotrope may have caused more arrhythmia deaths, although this wasn't a prespecified study end point.
Digoxin's effect on deterioration in clinical status was much more clearcut in the metaanalysis. The odds ratio for that end point was 0.31, meaning patients randomized to digoxin were 69% less likely to show significant clinical deterioration than were control patients.
Digoxin patients were 32% less likely to experience the end point of hospitalization for worsening heart failure.
Two studies included in the metaanalysis showed that patients on an ACE inhibitor plus digoxin did better than those on an ACE inhibitor plus placebo. However, the effects of digoxin in patients on other agents that have become first-line therapies in heart failure more recently than the ACE inhibitors, including β-blockers and aldosterone antagonists, haven't been systematically studied. For ethical reasons it's highly unlikely such trials will ever be done, Dr. Hood said.